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Natural History of Renal Artery Stenosis: When to Intervene
In conclusion, running a complete peripheral vascular service as an interventional radiologist is an obtainable goal. It does require persistence and a true commitment by everyone involved to establish the service and keep it going. Running the peripheral vascular service can make practice more rewarding and secure.
Wednesday, March 24, 1999 8:00-9:30 am Plenary Session-Renovascular Intervention Moderator: Scott O. Trerotola, MD 8:00 am
Natural History of Renal Artery Stenosis: When to Intervene
Marc A. Pohl, MD Cleveland Clinic Foundation Cleveland, Ohio Learning objectives: (1) To define the terms renal artery stenosis, renovascular hypertension, and ischemic nephropathy. (2) To review the pathophysiology ofreno-
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vascular hypertension. (3) To describe diagnostic maneuvers used to detect renal artery stenosis. (4) To describe the patients at risk for developing ischemic nephropathy. (5) To discuss management strategies and renal revascularization (surgical or endovascular) for patients with atherosclerotic renal artery stenosis. The major issues in approaching patients with atherosclerotic renal artery disease (ASO-RAD) relate to the role of renal artery disease (RAD) in the pathogenesis of hypertension (i.e., renovascular hypertension [RVHTJ), and to the potential for vascular compromise of renal function. Historically, surgical renal revascularization has been used widely as a therapeutic option to relieve presumed RVHT. More recendy, considerable interest and enthusiasm have been generated for surgical renal revascularization, percutaneous transluminal renal artery angioplasty (PTRA), and renal artery stenting to preserve renal function. Whether to use renal revascularization to improve blood pressure depends on the likelihood that intervention will improve the blood pressure. Clinical clues suggesting that renal revascularization will improve the blood pressure include hypertension onset before age 30 year or after 60 years; well-documented, abrupt onset of hypertension; acceleration of preViously stable and wellcontrolled blood pressure; hypertension refractory to an appropriate three-drug regimen; accelerated retinopathy; and the observation of a diastolic abdominal bruit (especially in patients with fibrous renal artery disease). In contrast, elderly patients with generalized atherosclerosis obliterans, a long duration of hypertension, increased serum creatinine concentration, and normal serum potassium values are unlikely to have RVHT. Diagnostic tests designed to detect the anatomic presence of RAD include renal artery duplex sonography,
magnetic resonance angiography, spiral computed tomography scanning, and captopril renography. Diagnostic tests suggesting that RAD may be instrumental in producing hypertension (i.e., RVHT) include radionuclide renal scanning with and without ACE inhibition (captopril renography), and selective renal vein renin determinations. When the goal of intervention in RAD is primarily to improve blood pressure control, the interventional strategy usually depends on whether the RAD is due to atherosclerosis or one of the fibrous dysplasias. For atherosclerotic lesions that involve the ostium, or that are associated with severe aortic atherosclerosis, aneurysm, or both, surgery is the preferred treatment. Palmaz stents to treat ostial renal artery stenosis are being used with improved technical success. If the RAD and presumed RVHT are caused by one of the fibrous dysplasias, particularly medial fibroplasia, PTRA is usually the interventional modality of choice. The observation of improved renal function after surgical renal revascularization is not new. In 1962, Morris and colleagues (1) described eight azotemic patients with bilateral renal artery stenosis who experienced improved renal function after surgical revascularization. However, the major indication for operation in this report was the presence of severe associated hypertension, because the concept of undertaking renal revascularization primarily to stabilize or improve renal function had not yet arisen. Additional reports in the 1960s and 1970s described improvement in renal function in patients undergoing renal revascularization for presumed RVHT. Although the benefiCial effect of surgery on renal function in these reports was, in part, attributable to improved blood pressure control, the possibility that improved renal perfusion pressure promoted an increased glomerular filtration rate was also entertained. Enthusiasm for the concept of renal revascularization to preserve or stabilize renal function increased on the heels of publications from the Cleveland Clinic (6) and from Boston University Medical Center (9). At about the same time, reports appeared indicating the potential benefit of PTRA to improve renal function in patients with ASO-RAD. Thus the potential threat to overall renal function posed by ASO-RAD became recognized as an important clinical issue, separate, and distinct from the problem of "renovascular hypertension." The syndrome of "ischemic renal disease" or "ischemic nephropathy" now loomed as an important clinical condition and has attracted the fascination of nephrologists, vascular surgeons, and interventional radiologists. Two definitions of ischemic nephropathy are suggested herein: 1) a clinically significant reduction in renal function caused by compromise of the renal circulation, and 2) clinically Significant reduction in the glomerular filtration rate caused by hemodynamically significant obstruction to renal blood flow or renal failure resulting from renal artery occlusive disease. Atherosclerotic RAD has been claimed to contribute
to end-stage renal disease. Surgical revascularization or renal artery stenting has ended the need for dialysis in some patients. Despite these rewarding anecdotes, most patients with ASO-RAD and end-stage renal failure have severe irreversible ischemic parenchymal damage that precludes recovery of renal function, even if main renal arterial blood flow is restored. Many of these patients have associated atheroembolic renal disease, severe small vessel disease (nephrosclerosis), or both, which limit the effectiveness of interventional maneuvers on the main renal artery (i.e., surgical or endovascular renal revascularization) to improve renal function. Underlying the concept of renal revascularization (surgical or endovascular) is the notion that ASO-RAD is a progressive disorder. Precise information on the natural history of ASO-RAD has not been obtained in prospective studies with serial renal angiography. However, in several carefully done retrospective studies, and in at least one prospective study of repeated renal duplex ultrasonography, ASO-RAS appears to be a progressive condition. Whether well-documented progressive ASORAS produces end-stage renal failure remains to be determined. Progressive atherosclerotic renal artery stenosis (ASO-RAS), with or without decrements in the overall glomerular filtration rate, is not synonymous with endstage renal disease. Adding to the temptation to detect ASO-RAS is the frequency with which ASO-RAS is observed in patients with generalized atherosclerosis obliterans, regardless of whether there is suspected RVHT. In a postmortem study, Holley et al (964), found moderate or severe stenosis of the renal artery in nearly 50% of patients who had been normotensive ante mortem. Dustan and colleagues (2) reported that 39 of III normotensive patients (35%) had unsuspected ASO-RAD in one or both renal arteries shown on aortography performed to evaluate peripheral arterial occlusive disease. More recently, Olin and associates (26) prospectively studied 395 consecutive patients who underwent arteriography for routine evaluation of abdominal aortic aneurysm, aortic occlusive disease, lower extremity occlUSive disease, and suspected RAS. More than 50% RAS was observed in 38% of patients with abdominal aortic aneurysm, in 33% with aortic occlusive disease, and in 39% with lower extremity atherosclerotic occlusive disease. High-grade RAS was observed in 13% of the patients studied. Landwehr et ai, and Harding et al. (32), demonstrated ASO-RAD in as many as 30% of patients with coronary arteIY disease. These observations indicate that ASO-RAD is frequently present as a complication of generalized atherosclerosis. In fact, the anatomic presence of ASO-RAD is far more common than ASO-RAD as a cause of hypertension (i.e., atherosclerotic RVHT). Various techniques exist to screen for ASO-RAD, such as DTPA renal scan, captopril renography, and more recently duplex ultrasonography. Duplex ultrasound scanning of the renal arteries is an excellent noninvasive screening test to detect renal a11ery stenosis. It combines
direct visualization of the renal arteries (B-mode imaging) with measurement of various hemodynamic factors in the main renal arteries and within the kidney (Doppler), thus prOViding anatomic and functional assessments. Duplex scanning also allows the simultaneous measurement of kidney size. Unlike other noninvasive tests, duplex scanning is not affected by medications the patients may be taking, the level of renal function, or whether the disease is unilateral or bilateral or affects a solitary functioning kidney. The advantage of duplex scanning of the renal arteries is that it is highly sensitive and specific for diagnosing significant renal arteIY disease. However, the technique is technically demanding and has a steep learning curve. Therefore, each vascular laboratory needs to correlate the results obtained from duplex ultrasound of the renal arteries with arteriography to ensure a reasonable degree of correlation. Accessory renal arteries are difficult to identify and remain a limitation of this test. With the advent of endovascular techniques to treat atherosclerotic renal artery stenosis (renal artery stenting and PTRA); duplex scanning is also an excellent test to follow patients serially who have undergone previous renal artery intervention. By performing surveillance duplex ultrasound examinations periodically (every 6-12 months), the radiologist can detect restenosis and intervene before the renal arteIY occludes. The impressive sensitiVity and specificity of duplex ultrasonography in screening for significant RAS has, in some centers, fueled enthusiasm to search for ASO-RAD. In addition, in some medical institutions and practices, patients with hypertension and suspected coronary arteIY disease undergo "routine" renal arteriography at the time of coronary al1eriography. Some of these patients also undergo PTRA at the same time. This prompts the question, Is the anatomic presence of ASO-RAD a mandate for intervention? The following case summary demonstrates the trends just described. A 62-year-old white diabetic man presented with signs and symptoms of claudication in the right leg and occasional rest pain. Hypertension had been present for 15 years and was controlled with 80 mg Inderal daily (Wyeth-Ayerst, Philadelphia, PA). The serum creatinine concentration was 1.1 mg/dl. Arteriography revealed a completely occluded right common iliac artery and 80% stenosis of the right renal artely. The left renal artery was Widely patent. A Dacron aortal femoral bypass graft was implanted as was a right i1iorenal graft. In considering patients as candidates for renal revascularization (surgical or endovascular) to preserve renal function, some determination should be made of the potential for salvaging renal function. HelpfUl clinical clues suggesting renal salvageability include a kidney size >9 cm (pole-to-pole length) by laminagraphy, some function of the kidney on a urogram or renal flow scan, filling of the distal renal arteries (by collaterals) angiographically when the main renal artery is completely occluded proximally, and a renal biopsy that shows
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Table 1 Ischemic Renal Disease: Outcome of Angioplasty
Investigator and Year
Patients (n)
Luft, 1983 Pickering, 1986 Bell, 1987 O'Donovan, 1992 Total
12 55 20 17
104
Angioplasty Outcome, n (%) Improved
Stable
Worse"
Death
3 (25) 26 (47) 7 (35) 9 (53) 45 (43)
5 (42) 19 (35) 10 (50) 2(12) 36 (35)
4 (33) 10 (18) 3 (15) 6 (35) 23 (22)
0(0) NA 0(0) 5 (29) 5 (5)
* Includes all deaths. NA ~ not available. Modified from Rimmer JM, Gennari FJ. Ann Intern Med 1993;118:712--719. Table 2 Ischemic Renal Disease: Outcome of Surgery
Investigator and Year
Patients (n)
Luft, 1983 Jamieson, 1984 Novick, 1987 Hansen, 1989 Messina, 1992 Bredenberg, 1992 Libertino, 1992 Total
12 23 153 25 17
25 97 352
Surgical Outcome, n (%) Improved
Stable
Worse"
Death
8 (67) 15 (65) 93 (61) 12 (48) 12 (71) 9 (36) 45 (46) 194 (55)
2 (17) 0(0) 50 (33) 11 (44) 2 (12) 12 (48) 31 (32) 108 (31)
2 (17) 8 (35) 10 (6) 2 (8) 3 (18) 4 (16) 21 (22) 50 (14)
2 (17) 4 (17) 5 (3) 2 (8) 1 (6) NA 6 (60) 20 (6)
• Includes all deaths. NA = not available. Adapted from Rimmer JM, Gennari FJ. Ann Intern Med 1993;118:712-719.
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well-preserved glomeruli with minimal interstitial scarring. Patients with moderately severe azotemia (i.e., serum creatinine values >3 or 4 mg/dO are likely to have severe renal parenchymal disease that renders improvement in renal function after renal revascularization unlikely. Exceptions to this observation are cases of total main renal artery occlusion wherein kidney viability is maintained through the collateral circulation. Sometimes a kidney biopsy may help guide subsequent decision making regarding renal revascularization for the goal of improving kidney function. In addition, most candidates for renal revascularization, when RAS is caused by atherosclerosis, have some degree of renal insufficiency. Whether the renal insufficiency is attributable to RAS, nephrosclerosis, or atheroembolic renal artery disease (not uncommon in this population) frequently is difficult to determine. Therefore, the term "ischemic nephropathy" is almost certainly more complex than being due simply to atherosclerotic renal artery stenosis. In addition, in the azotemic patient with ASO-RAD, other potential causes or contributors to the azotemia must be excluded, such as obstructive uropathy (e.g., benign prostatic hypertrophy); primary glomerular disease (suggested by heavy proteinuria), which will progress at its own inherent pace; drugrelated renal insufficiency (e.g., from nonsteroidal antiinflammatory drugs); and uncontrolled blood pressure. If the physician chooses to intervene in ASO-RAD with the goal of preserving renal function with either surgical or endovascular renal revascularization, he or
she must appreciate that these patients are at high risk for intervention because of age and frequently associated coronary, cerebrovascular, peripheral vascular disease (or all three). Their aortas are often laden with extensive atherosclerotic plaque, making angiographic investigation, PTRA, or renal artery stenting hazardous. Technical difficulties or complications of angiographic intervention, PTRA, and renal artery stenting in these patients include contrast media acute renal failure and atheroembolic renal disease. Spontaneous atheroembolic renal disease or atheroembolic renal disease associated with angiography or PTRA is not uncommon in this patient group. Coexisting coronary and cerebrovascular atherosclerotic disease are additional risk factors for these patients when major visceral vascular surgery is considered. Despite these risks, the olltcome of surgery for ischemic renal disease has been encouraging. Treatment is directed toward preserving renal function, improving of renal function, and sometimes weaning patients from dialysis. Because hypertension is nearly always present in these patients, treatment frequently produces marked improvement in blood pressure control. Published studies on treatment results in ischemic renal disease are not as numerous as studies on RVHT. However, the available data suggest that surgical revascularization has an advantage over PTRA. A summary of the published studies on outcomes of angioplasty and surgery in ischemic renal disease are listed in Tables 1 and 2. The morbidity and mortality rates in such patients
have been minimized by selective screening, correction of significant existing coronary and cerebrovascular disease, or both before undertaking elective surgical renal revascularization for ASO-RAD. Various surgical revascularization techniques are available to treat patients with significant renal artery disease. Aortorenal bypass with a free autogenous hypogastric artery or saphenous vein remains a popular method in patients with a nondiseased abdominal aorta. Polytetrafluoroethylene aortorenal bypass grafts have been used successfully by some authors, usually when an autogenous graft is not available. Renal endarterectomy also continues to ~be used to treat atherosclerotic renal artery disease. Patients with complex branch renal artery lesions are managed with extracorporeal microvascular reconstruction and autotransplantation. In older patients, severe atherosclerosis of the abdominal aorta may render an aortorenal bypass or endarterectomy technically difficult and potentially hazardous. In such cases, several authors prefer alternative surgical approaches that allow renal revascularization to be accomplished safely and effectively while avoiding operation on a badly diseased aorta. The most effective alternate bypass techniques have been a splenorenal bypass for left renal revascularization and a hepatorenal bypass for right renal revascularization. The absence of occlusive disease involving the origin of the celiac artery is an important prerequisite for these operations. A recent study indicated the presence of significant celiac artery stenosis in 50% of patients with atherosclerotic renal artery stenosis. This information underscores the importance of obtaining preoperative lateral aortography to evaluate the celiac artery origin in patients who are being considered for hepatorenal or splenorenal bypass. Use of the supraceliac or lower thoracic aorta for renal revascularization is a new surgical alternative in patients with significant atherosclerosis of the abdominal aorta and its major visceral branches. The supraceliac aorta is often relatively disease free in such patients and can be used to achieve renal vascular reconstruction with an interposition saphenous vein graft. Simultaneous aortic replacement and renal revascularization have been associated with an increased risk for operative death, and this approach is best reserved for patients with a fixed indication for aortic replacement, such as a significant aortic aneurysm or symptomatic aortoiliac occlusive disease. Because percutaneous transluminal renal angioplasty has a suboptimal long-term benefit for atherosclerotic ostial renal artery stenosis, several groups of investigators have used endovascular stenting for ostial renal artery stenosis. In an initial series reported by Rees and colleagues (Palmaz stent and atherosclerotic renal artery stenosis involving the ostium of the renal arteries: Preliminary report of a multicenter study. Radiology 1991; 181:507), technical success was achieved in 27 of 28 patients. Sixty-four percent of patients had blood pres-
sure cured or improved and 10 of 14 patients had stabilization of renal function. However, restenosis occurred in 7 of the 18 patients studied (39%). More recently, Blum and colleagues (48) reported impressive technical results and long-term patency rates in the treatment of ostial renal stenoses with vascular endoprostheses after unsuccessful balloon angioplasty. Investigators at the Cleveland Clinic have performed renal artery stents for atherosclerotic renal artery stenosis in approximately 120 patients. We previously described 77 patients (98 renal arteries), and our technical success rate was 98%. At times we used intravascular ultrasound to ensure adequate deployment of the stent. The mean clinical follow-up period was 13.8 months, with a maximum follow-up of 36.5 months. The 6-month patency rate by angiography and ultrasound was 95%, and the 12-month patency rate was 82.2%. When restenosis was identified by routine duplex ultrasound surveillance studies, the patients underwent repeated arteriography, and the stent was reexpanded if Significant stenosis was present. The primary assisted patency rate was 100%. Blood pressure was improved in approximately 85% of patients. Renal function improved in 35% of patients, remained stable in 35% of patients, and worsened in 30% of patients. The complication rate associated with the procedure involved nine pseudoaneurysms. Seven of the nine were repaired by ultrasound-guided compression repair. Four patients developed acute tubular necrosis, none of whom required dialysis. Three patients had clinically Significant atheromatous embolization. It is unclear what the long-term restenosis rate will be for renal artery stenting for ostial disease. However, some investigators believe the results will be improved by overexpanding the renal altery stent and using intraarterial ultrasound to ensure that the stent is properly deployed. It is important to allow the stent to extend into the aorta 1 or 2 mm in patients with ostial disease. Renal artery stenting is an excelJent procedure for patients with advanced atherosclerosis who are at high risk for surgical revascularization. Clearly, the technology for diagnosing ASO-RAD has advanced considerably. Surgical and endovascular methods for renal revascularization have been used with a high degree of technical success in some medical centers. Despite these observations, and the increasing enthusiasm for renal revascularization to avert or reverse renal insufficiency, the hypothesis that ASO-RAD progresses in most patients, despite adequate blood pressure control, with resulting loss of renal function, and that overall renal function can be preserved in the long term by successful renal revascularization remains unproved. A single-center prospective controlled clinical trial is in progress at the Cleveland Clinic, which eventually may determine whether ASO-RAD is a correctable cause of renal failure. Finally, several unresolved issues remain regarding the wide-spread application of interventional approaches to these patients: Can we be certain that
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ASO-RAD is, indeed, a progressive disorder? What is the optimal time to intervene to preserve renal function in patients with progressive azotemia? That is, is there a window of opportunity within which one should intervene, and at what point is it too early or too late to intervene? In patients with controlled blood pressure and mild degrees of renal insufficiency, is an aggressive approach to preserve renal function justified? Considering the risks involved with such patients, should our attention be directed to detecting and treating ASO-RAD with a view toward removing patients from dialysis Cend-stage renal disease) rather than to intervening under the assumption that nonoperated or nondilated ASO-RAD eventually will progress to renal insufficiency and end-stage renal disease' Finally, how many patients are actually receiving dialysis consequent to ASO-RAD? Although the information reviewed herein suggests a favorable influence of interventional therapy on the natural history of ASO-RAD, future studies in this area must include controlled clinical trials that compare patients with similar degrees of ASO-RAD managed concurrently with nonoperative therapy. Prospective evaluations of P1'RA and renal artery stents and surgical revascularization should be evaluated and compared rigorously.
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26. Olin JW, et at. Prevalence of atherosclerotic renal artery stenosis in patients with atherosclerosis elsewhere. Am] Med 1990; 88:46N-51N. 27. Dean RH, Tribble RW, Hansen K], O'Neil E, Craven TE, ReddingJF: Evolution of renal insufficiency in ischemic nephropathy. Ann Surg 1991; 213:446-456. 28. Main], Wilkinson R: Angioplasty for atheromatous renal artery stenosis. Do the benefits outweigh the risks'] Nephrol 1991; 3:143-146. 29. Pohl MA, Horner C, Goormastic M, Novick A: Does renal revascularization preserve renal function in patients with atherosclerotic renal artery stenosis? An ongoing prospective study [Abstract]. ] Am Soc Nephrol 1991; 2:242. 30. Sos TA: Angioplasty for the treatment of azotemia and renovascular hypertension in atherosclerotic renal artery disease. Circulation 1991; 83(S-0:I-162-I166. 31. Hansen K], Starr SM, Sands RE, et at. Contemporary surgical management of renovascular disease.] Vasc Surg 1992; 16:319-330 [with a discussion on p 330]. 32. Harding MB, Smith LR, Himmelstein SI, et at. Renal artelY stenosis: prevalence and associated risk factors in patients undergoing routine cardiac catheterization.] Am Soc Nephrol 1992; 2:]608-1616. 33. Rimmer ]M, Gennari J. Atherosclerotic renovascular disease and progressive renal failure. Ann Intern Med 1993; 118:712-719. 34. Weibull H, Bergqvist D, Bergentz SE, et at. Percutaneous transluminal renal angioplasty versus surgical reconstruction of atherosclerotic renal artery stenosis: a prospective randomized study. ] Vasc Surg 1993; 18:841-850 [with a discussion on pp 850-8521. 35. Bacharach ]M, Olin JW, Graor RA, et at. Stenting of the renal arteries for atherosclerotic renal artery stenosis. Presented to the American College of Cardiology, Atlanta, Georgia, March 13-17, 1994. 36. Cambria RP, Brewster DC, L'Italien G], et al. The durability of different reconstructive techniques for atherosclerotic renal artery disease.] Vasc Surg ]994; 20:76-85 [with a discussion on pp 86-87]. 37. Hansen KJ. Prevalence of ischemic nephropathy in the atherosclerotic population. Am J Kid Dis ]994; 24:615-621. 38. Mailloux LU, et at. Renovascular disease causing end-stage renal disease, incidence, clinical correlates and outcomes: a 20 year clinical experience. Am J Kid Dis 1994; 24:622-629.
41. Clair DG, Belkin M, Whittemore AD, et al. Safety and efficacy of transaortic renal endalterectomy as an adjunct to aortic surgely. ] Vasc Surg 1995; 21:926-33 [with a discussion on p 934]. 42. Hansen KJ, et at. Surgical management of dialysisdependent ischemic nephropathy. J Vasc Surg 1995; 21:197-211. 43. Olin JW, et al. The utility of duplex scanning of the renal arteries for diagnosing significant renal artery stenosis. Ann Intern Med 1995; 122:833-838. 44. Topol EJ, Nissen SE. Our preoccupation with coronary luminology; the dissociation between clinical and angiographic findings in ischemic heart disease. Circulation 1995; 92:2333-2342. 45. Cambria RP, Brewster DC, L'ltalien GJ, et al. Renal artery reconstruction for the preservation of renal function. J Vasc Surg 1996; 24:37]-80 [with a discussion on pp 380-382]. 46. Erdoes LS, Berman SS, Hunter GC, MiJls JL. Comparative analysis of percutaneous transluminal angioplasty and operation for renal revascularization. Am J Kidney Dis 1996; 27:496-503. 47. Zierler RE, Bergelin RO, Davidson RC, et at. A prospective study of disease progression in patients with atherosclerotic renal artery stenosis. Am] Hypertens 1996; 9:1055-1061. 48. Blum U, Krumme B, Flugel P, et at. Treatment of ostial renal-artelY stenoses with vascular endoprostheses after unsuccessful baJloon angioplasty. N Engl J Med 1997; 336:459-465. 49. Harden PN, Macleod M], Rodger RSC, et al. Effect of renal-artery stenting on progression of renovascular renal failure. Lancet 1997; 349;1133-1136. 50. Pohl MA. Renal artery stenosis, renal vascular hypertension and ischemic nephropathy. In Schrier RW, Gottschalk CW, eds. Diseases of the Kidney, 6th ed. Boston: Little, Brown and Company, 1997, pp 13671425 51. Tullis MJ, Zierler RE, Glickerman DJ, et at. Results of percutaneous transluminal angioplasty for atherosclerotic renal artery stenosis: a follow-up study with duplex ultrasonography.] Vasc Surg 1997; 25:46-54. 52. Caps MT, Zierler RE, Polissar NL, et al. Risk of atrophy in kidneys with atherosclerotic renal artery stenosis. Kidney Int 1998; 53:735-742. 53. Fiala LA, Jackson MR, GiJlespie DL, et at. Primary stenting of atherosclerotic renal artery ostial stenosis. Ann Vasc Surg 1998; 12:128-133.
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54. Plouin PF, Chatellier G, Dame B, Raynaud A, for the Essai Multicentrique Medicaments vs. Angioplastie (EMMA) Study Group. Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a randomized trial. Hypertension 1998; 31:823-829. 55. Textor Sc. Revasularization in atherosclerotic renal artery disease. Kidney Int 1998: 53:799-811. 56. van de Yen P]G, Beutler ]], Katee R, et al. Angiotensin converting enzyme inhibitor-induced renal dysfunction in atherosclerotic renovascular disease. Kidney Int 1998; 53:986-993. 8:20 am Noninvasive Diagnosis of Renal Artery Stenosis: Which Test to Use When Berrzard F. King, Jr., MD Mayo Clinic Rochester, Minnesota
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Learning objectives: (1) List thefour noninvasive techniques being used for the evaluation of renovascular hypertension; (2) Give the strengths and weaknesses of captopril renography in the evaluation of renovascular hypertension; (3) Give the strengths and weaknesses of color Doppler sonography in the evaluation of renovascular hypertension; (4) Give the strengths and weaknesses of CT angiography in the evaluation of renovascular hypertension; (5) Give the strengths and weaknesses ofMR angiography in the evaluation of renovascular hypertension. More than 50 million people in the United States are hypertensive. Renovascular disease may account for up to 5% of these hypertensive patients. Because renovascular hypertension is potentially curable, much effort has been devoted to detecting and treating patients with renal artery stenosis. Conventional angiography traditionally has been used to diagnose renal artery stenosis; because of its invasiveness and cost, however, conventional angiography usually is not used as a screening test in all patients who may have renal artery stenoses. Several noninvasive studies have been advocated for screening patients who may have renovascular hypertension. The most commonly used noninvasive screening examination techniques include Doppler sonography, captopril renography, computed tomographic (CT) angiography, and magnetic resonance (MR) angiography. Because the accuracy of these noninvasive studies is widely variable, a proper understanding and appropriate use of these noninvasive studies is mandatory. Choosing the appropriate noninvasive screening imaging study for renovascular disease begins with proper clinical evaluation. No single clinical finding is capable of consistently identifying patients with renovascular hypertension; however, several risk factors can suggest the possibility of renovascular disease. These include onset of hypertension under the age of 30 or after the age of 50, abrupt onset at any time, hypertension refractory to medical therapy, grade 3 or 4 retinopathy, epigastric
bruit, deterioration of renal function after angiotensin converting enzyme (ACE) inhibitor therapy, and generalized arterial sclerotic disease with hypertension. Proper identification of these clinical findings can lead to more advantageous use of noninvasive screening examinations for renovascular hypertension. Duplex Doppler Sonography Duplex Doppler sonography is an attractive noninvasive screening test because it is relatively inexpensive, does not require intravascular contrast medium, and can be used in patients with any level of renal function. As with many of the noninvasive imaging examinations, there have been numerous reported parameters and abnormal criteria indicating possible renovascular disease. The most often quoted parameters are peak systolic velocities in the renal artery exceeding 100-200 crn/sec or a renal artery/aortic peak systolic velocity ratio exceeding 3.5. By using these parameters, early investigators have quoted sensitivities from 85% to 90%. Specificities were also quite high, in the range of 95%. However, many investigators have had trouble duplicating these results, and some have reported extremely poor sensitivity, as low as 0%. A major problem in many of these studies is that approximately 10% to 20% of patients undergoing duplex Doppler exams of the renal arteries have technically inadequate studies secondary to obesity or overlying bowel gas. These patients often are eliminated from statistical analysis in the aforementioned studies. In addition, examinations reported in various studies have varied in length, from 10 to 15 minutes up to 90 minutes. This variability in examination time, technical expertise, and super-selection of patients has contributed to the variability in sensitivity rates reported in the literature. Recent reports have advocated velocity waveform analysis of the segmental renal arteries in the kidneys. These smaller vessels are more consistently identified through a flank approach, allOWing for a consistent exam even in obese patients and in patients with anterior abdominal bowel gas. By using upper, middle, and lower pole segmental artery velocity waveform analysis in the kidneys, one can evaluate the waveform appearance and determine if there is a dampened peak systolic velocity (parva) or a delay in peak systolic velocity (tarda). If the parva and/or tarda waveform occurs in these segmental arteries, it indicates a more prOXimal artery stenosis. Early reports demonstrated a sensitivity of 85% to 90% in the detection of renal artery stenosis using these segmental artery waveform analyses. Subsequent studies, however, have not been able to duplicate such high sensitivities with this technique. It now appears evident that Doppler sonographic analysis of the renal arteries for the detection of renal artery stenosis should include velocity waveform analysis of both the main renal artery and the segmental renal arteries in both kidneys. Combining both the main renal artery and segmental altery waveform analysis will offer the highest sensitivity in .the detection of renal artery
Wednesday, March 24, 1999 8:00-9:30 am Plenary Session-Renovascular Intervention Moderator: Scott O. Trerotola, MD 8:00 am
Natural History of Renal Artery Stenosis: When to Intervene
Marc A. Pohl, MD Cleveland Clinic Foundation Cleveland, Ohio Learning objectives: (1) To define the terms renal artery stenosis, renovascular hypertension, and ischemic nephropathy. (2) To review the pathophysiology ofreno-
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vascular hypertension. (3) To describe diagnostic maneuvers used to detect renal artery stenosis. (4) To describe the patients at risk for developing ischemic nephropathy. (5) To discuss management strategies and renal revascularization (surgical or endovascular) for patients with atherosclerotic renal artery stenosis. The major issues in approaching patients with atherosclerotic renal artery disease (ASO-RAD) relate to the role of renal artery disease (RAD) in the pathogenesis of hypertension (i.e., renovascular hypertension [RVHTJ), and to the potential for vascular compromise of renal function. Historically, surgical renal revascularization has been used widely as a therapeutic option to relieve presumed RVHT. More recendy, considerable interest and enthusiasm have been generated for surgical renal revascularization, percutaneous transluminal renal artery angioplasty (PTRA), and renal artery stenting to preserve renal function. Whether to use renal revascularization to improve blood pressure depends on the likelihood that intervention will improve the blood pressure. Clinical clues suggesting that renal revascularization will improve the blood pressure include hypertension onset before age 30 year or after 60 years; well-documented, abrupt onset of hypertension; acceleration of preViously stable and wellcontrolled blood pressure; hypertension refractory to an appropriate three-drug regimen; accelerated retinopathy; and the observation of a diastolic abdominal bruit (especially in patients with fibrous renal artery disease). In contrast, elderly patients with generalized atherosclerosis obliterans, a long duration of hypertension, increased serum creatinine concentration, and normal serum potassium values are unlikely to have RVHT. Diagnostic tests designed to detect the anatomic presence of RAD include renal artery duplex sonography,
magnetic resonance angiography, spiral computed tomography scanning, and captopril renography. Diagnostic tests suggesting that RAD may be instrumental in producing hypertension (i.e., RVHT) include radionuclide renal scanning with and without ACE inhibition (captopril renography), and selective renal vein renin determinations. When the goal of intervention in RAD is primarily to improve blood pressure control, the interventional strategy usually depends on whether the RAD is due to atherosclerosis or one of the fibrous dysplasias. For atherosclerotic lesions that involve the ostium, or that are associated with severe aortic atherosclerosis, aneurysm, or both, surgery is the preferred treatment. Palmaz stents to treat ostial renal artery stenosis are being used with improved technical success. If the RAD and presumed RVHT are caused by one of the fibrous dysplasias, particularly medial fibroplasia, PTRA is usually the interventional modality of choice. The observation of improved renal function after surgical renal revascularization is not new. In 1962, Morris and colleagues (1) described eight azotemic patients with bilateral renal artery stenosis who experienced improved renal function after surgical revascularization. However, the major indication for operation in this report was the presence of severe associated hypertension, because the concept of undertaking renal revascularization primarily to stabilize or improve renal function had not yet arisen. Additional reports in the 1960s and 1970s described improvement in renal function in patients undergoing renal revascularization for presumed RVHT. Although the benefiCial effect of surgery on renal function in these reports was, in part, attributable to improved blood pressure control, the possibility that improved renal perfusion pressure promoted an increased glomerular filtration rate was also entertained. Enthusiasm for the concept of renal revascularization to preserve or stabilize renal function increased on the heels of publications from the Cleveland Clinic (6) and from Boston University Medical Center (9). At about the same time, reports appeared indicating the potential benefit of PTRA to improve renal function in patients with ASO-RAD. Thus the potential threat to overall renal function posed by ASO-RAD became recognized as an important clinical issue, separate, and distinct from the problem of "renovascular hypertension." The syndrome of "ischemic renal disease" or "ischemic nephropathy" now loomed as an important clinical condition and has attracted the fascination of nephrologists, vascular surgeons, and interventional radiologists. Two definitions of ischemic nephropathy are suggested herein: 1) a clinically significant reduction in renal function caused by compromise of the renal circulation, and 2) clinically Significant reduction in the glomerular filtration rate caused by hemodynamically significant obstruction to renal blood flow or renal failure resulting from renal artery occlusive disease. Atherosclerotic RAD has been claimed to contribute
to end-stage renal disease. Surgical revascularization or renal artery stenting has ended the need for dialysis in some patients. Despite these rewarding anecdotes, most patients with ASO-RAD and end-stage renal failure have severe irreversible ischemic parenchymal damage that precludes recovery of renal function, even if main renal arterial blood flow is restored. Many of these patients have associated atheroembolic renal disease, severe small vessel disease (nephrosclerosis), or both, which limit the effectiveness of interventional maneuvers on the main renal artery (i.e., surgical or endovascular renal revascularization) to improve renal function. Underlying the concept of renal revascularization (surgical or endovascular) is the notion that ASO-RAD is a progressive disorder. Precise information on the natural history of ASO-RAD has not been obtained in prospective studies with serial renal angiography. However, in several carefully done retrospective studies, and in at least one prospective study of repeated renal duplex ultrasonography, ASO-RAS appears to be a progressive condition. Whether well-documented progressive ASORAS produces end-stage renal failure remains to be determined. Progressive atherosclerotic renal artery stenosis (ASO-RAS), with or without decrements in the overall glomerular filtration rate, is not synonymous with endstage renal disease. Adding to the temptation to detect ASO-RAS is the frequency with which ASO-RAS is observed in patients with generalized atherosclerosis obliterans, regardless of whether there is suspected RVHT. In a postmortem study, Holley et al (964), found moderate or severe stenosis of the renal artery in nearly 50% of patients who had been normotensive ante mortem. Dustan and colleagues (2) reported that 39 of III normotensive patients (35%) had unsuspected ASO-RAD in one or both renal arteries shown on aortography performed to evaluate peripheral arterial occlusive disease. More recently, Olin and associates (26) prospectively studied 395 consecutive patients who underwent arteriography for routine evaluation of abdominal aortic aneurysm, aortic occlusive disease, lower extremity occlUSive disease, and suspected RAS. More than 50% RAS was observed in 38% of patients with abdominal aortic aneurysm, in 33% with aortic occlusive disease, and in 39% with lower extremity atherosclerotic occlusive disease. High-grade RAS was observed in 13% of the patients studied. Landwehr et ai, and Harding et al. (32), demonstrated ASO-RAD in as many as 30% of patients with coronary arteIY disease. These observations indicate that ASO-RAD is frequently present as a complication of generalized atherosclerosis. In fact, the anatomic presence of ASO-RAD is far more common than ASO-RAD as a cause of hypertension (i.e., atherosclerotic RVHT). Various techniques exist to screen for ASO-RAD, such as DTPA renal scan, captopril renography, and more recently duplex ultrasonography. Duplex ultrasound scanning of the renal arteries is an excellent noninvasive screening test to detect renal a11ery stenosis. It combines
direct visualization of the renal arteries (B-mode imaging) with measurement of various hemodynamic factors in the main renal arteries and within the kidney (Doppler), thus prOViding anatomic and functional assessments. Duplex scanning also allows the simultaneous measurement of kidney size. Unlike other noninvasive tests, duplex scanning is not affected by medications the patients may be taking, the level of renal function, or whether the disease is unilateral or bilateral or affects a solitary functioning kidney. The advantage of duplex scanning of the renal arteries is that it is highly sensitive and specific for diagnosing significant renal arteIY disease. However, the technique is technically demanding and has a steep learning curve. Therefore, each vascular laboratory needs to correlate the results obtained from duplex ultrasound of the renal arteries with arteriography to ensure a reasonable degree of correlation. Accessory renal arteries are difficult to identify and remain a limitation of this test. With the advent of endovascular techniques to treat atherosclerotic renal artery stenosis (renal artery stenting and PTRA); duplex scanning is also an excellent test to follow patients serially who have undergone previous renal artery intervention. By performing surveillance duplex ultrasound examinations periodically (every 6-12 months), the radiologist can detect restenosis and intervene before the renal arteIY occludes. The impressive sensitiVity and specificity of duplex ultrasonography in screening for significant RAS has, in some centers, fueled enthusiasm to search for ASO-RAD. In addition, in some medical institutions and practices, patients with hypertension and suspected coronary arteIY disease undergo "routine" renal arteriography at the time of coronary al1eriography. Some of these patients also undergo PTRA at the same time. This prompts the question, Is the anatomic presence of ASO-RAD a mandate for intervention? The following case summary demonstrates the trends just described. A 62-year-old white diabetic man presented with signs and symptoms of claudication in the right leg and occasional rest pain. Hypertension had been present for 15 years and was controlled with 80 mg Inderal daily (Wyeth-Ayerst, Philadelphia, PA). The serum creatinine concentration was 1.1 mg/dl. Arteriography revealed a completely occluded right common iliac artery and 80% stenosis of the right renal artely. The left renal artery was Widely patent. A Dacron aortal femoral bypass graft was implanted as was a right i1iorenal graft. In considering patients as candidates for renal revascularization (surgical or endovascular) to preserve renal function, some determination should be made of the potential for salvaging renal function. HelpfUl clinical clues suggesting renal salvageability include a kidney size >9 cm (pole-to-pole length) by laminagraphy, some function of the kidney on a urogram or renal flow scan, filling of the distal renal arteries (by collaterals) angiographically when the main renal artery is completely occluded proximally, and a renal biopsy that shows
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Table 1 Ischemic Renal Disease: Outcome of Angioplasty
Investigator and Year
Patients (n)
Luft, 1983 Pickering, 1986 Bell, 1987 O'Donovan, 1992 Total
12 55 20 17
104
Angioplasty Outcome, n (%) Improved
Stable
Worse"
Death
3 (25) 26 (47) 7 (35) 9 (53) 45 (43)
5 (42) 19 (35) 10 (50) 2(12) 36 (35)
4 (33) 10 (18) 3 (15) 6 (35) 23 (22)
0(0) NA 0(0) 5 (29) 5 (5)
* Includes all deaths. NA ~ not available. Modified from Rimmer JM, Gennari FJ. Ann Intern Med 1993;118:712--719. Table 2 Ischemic Renal Disease: Outcome of Surgery
Investigator and Year
Patients (n)
Luft, 1983 Jamieson, 1984 Novick, 1987 Hansen, 1989 Messina, 1992 Bredenberg, 1992 Libertino, 1992 Total
12 23 153 25 17
25 97 352
Surgical Outcome, n (%) Improved
Stable
Worse"
Death
8 (67) 15 (65) 93 (61) 12 (48) 12 (71) 9 (36) 45 (46) 194 (55)
2 (17) 0(0) 50 (33) 11 (44) 2 (12) 12 (48) 31 (32) 108 (31)
2 (17) 8 (35) 10 (6) 2 (8) 3 (18) 4 (16) 21 (22) 50 (14)
2 (17) 4 (17) 5 (3) 2 (8) 1 (6) NA 6 (60) 20 (6)
• Includes all deaths. NA = not available. Adapted from Rimmer JM, Gennari FJ. Ann Intern Med 1993;118:712-719.
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well-preserved glomeruli with minimal interstitial scarring. Patients with moderately severe azotemia (i.e., serum creatinine values >3 or 4 mg/dO are likely to have severe renal parenchymal disease that renders improvement in renal function after renal revascularization unlikely. Exceptions to this observation are cases of total main renal artery occlusion wherein kidney viability is maintained through the collateral circulation. Sometimes a kidney biopsy may help guide subsequent decision making regarding renal revascularization for the goal of improving kidney function. In addition, most candidates for renal revascularization, when RAS is caused by atherosclerosis, have some degree of renal insufficiency. Whether the renal insufficiency is attributable to RAS, nephrosclerosis, or atheroembolic renal artery disease (not uncommon in this population) frequently is difficult to determine. Therefore, the term "ischemic nephropathy" is almost certainly more complex than being due simply to atherosclerotic renal artery stenosis. In addition, in the azotemic patient with ASO-RAD, other potential causes or contributors to the azotemia must be excluded, such as obstructive uropathy (e.g., benign prostatic hypertrophy); primary glomerular disease (suggested by heavy proteinuria), which will progress at its own inherent pace; drugrelated renal insufficiency (e.g., from nonsteroidal antiinflammatory drugs); and uncontrolled blood pressure. If the physician chooses to intervene in ASO-RAD with the goal of preserving renal function with either surgical or endovascular renal revascularization, he or
she must appreciate that these patients are at high risk for intervention because of age and frequently associated coronary, cerebrovascular, peripheral vascular disease (or all three). Their aortas are often laden with extensive atherosclerotic plaque, making angiographic investigation, PTRA, or renal artery stenting hazardous. Technical difficulties or complications of angiographic intervention, PTRA, and renal artery stenting in these patients include contrast media acute renal failure and atheroembolic renal disease. Spontaneous atheroembolic renal disease or atheroembolic renal disease associated with angiography or PTRA is not uncommon in this patient group. Coexisting coronary and cerebrovascular atherosclerotic disease are additional risk factors for these patients when major visceral vascular surgery is considered. Despite these risks, the olltcome of surgery for ischemic renal disease has been encouraging. Treatment is directed toward preserving renal function, improving of renal function, and sometimes weaning patients from dialysis. Because hypertension is nearly always present in these patients, treatment frequently produces marked improvement in blood pressure control. Published studies on treatment results in ischemic renal disease are not as numerous as studies on RVHT. However, the available data suggest that surgical revascularization has an advantage over PTRA. A summary of the published studies on outcomes of angioplasty and surgery in ischemic renal disease are listed in Tables 1 and 2. The morbidity and mortality rates in such patients
have been minimized by selective screening, correction of significant existing coronary and cerebrovascular disease, or both before undertaking elective surgical renal revascularization for ASO-RAD. Various surgical revascularization techniques are available to treat patients with significant renal artery disease. Aortorenal bypass with a free autogenous hypogastric artery or saphenous vein remains a popular method in patients with a nondiseased abdominal aorta. Polytetrafluoroethylene aortorenal bypass grafts have been used successfully by some authors, usually when an autogenous graft is not available. Renal endarterectomy also continues to ~be used to treat atherosclerotic renal artery disease. Patients with complex branch renal artery lesions are managed with extracorporeal microvascular reconstruction and autotransplantation. In older patients, severe atherosclerosis of the abdominal aorta may render an aortorenal bypass or endarterectomy technically difficult and potentially hazardous. In such cases, several authors prefer alternative surgical approaches that allow renal revascularization to be accomplished safely and effectively while avoiding operation on a badly diseased aorta. The most effective alternate bypass techniques have been a splenorenal bypass for left renal revascularization and a hepatorenal bypass for right renal revascularization. The absence of occlusive disease involving the origin of the celiac artery is an important prerequisite for these operations. A recent study indicated the presence of significant celiac artery stenosis in 50% of patients with atherosclerotic renal artery stenosis. This information underscores the importance of obtaining preoperative lateral aortography to evaluate the celiac artery origin in patients who are being considered for hepatorenal or splenorenal bypass. Use of the supraceliac or lower thoracic aorta for renal revascularization is a new surgical alternative in patients with significant atherosclerosis of the abdominal aorta and its major visceral branches. The supraceliac aorta is often relatively disease free in such patients and can be used to achieve renal vascular reconstruction with an interposition saphenous vein graft. Simultaneous aortic replacement and renal revascularization have been associated with an increased risk for operative death, and this approach is best reserved for patients with a fixed indication for aortic replacement, such as a significant aortic aneurysm or symptomatic aortoiliac occlusive disease. Because percutaneous transluminal renal angioplasty has a suboptimal long-term benefit for atherosclerotic ostial renal artery stenosis, several groups of investigators have used endovascular stenting for ostial renal artery stenosis. In an initial series reported by Rees and colleagues (Palmaz stent and atherosclerotic renal artery stenosis involving the ostium of the renal arteries: Preliminary report of a multicenter study. Radiology 1991; 181:507), technical success was achieved in 27 of 28 patients. Sixty-four percent of patients had blood pres-
sure cured or improved and 10 of 14 patients had stabilization of renal function. However, restenosis occurred in 7 of the 18 patients studied (39%). More recently, Blum and colleagues (48) reported impressive technical results and long-term patency rates in the treatment of ostial renal stenoses with vascular endoprostheses after unsuccessful balloon angioplasty. Investigators at the Cleveland Clinic have performed renal artery stents for atherosclerotic renal artery stenosis in approximately 120 patients. We previously described 77 patients (98 renal arteries), and our technical success rate was 98%. At times we used intravascular ultrasound to ensure adequate deployment of the stent. The mean clinical follow-up period was 13.8 months, with a maximum follow-up of 36.5 months. The 6-month patency rate by angiography and ultrasound was 95%, and the 12-month patency rate was 82.2%. When restenosis was identified by routine duplex ultrasound surveillance studies, the patients underwent repeated arteriography, and the stent was reexpanded if Significant stenosis was present. The primary assisted patency rate was 100%. Blood pressure was improved in approximately 85% of patients. Renal function improved in 35% of patients, remained stable in 35% of patients, and worsened in 30% of patients. The complication rate associated with the procedure involved nine pseudoaneurysms. Seven of the nine were repaired by ultrasound-guided compression repair. Four patients developed acute tubular necrosis, none of whom required dialysis. Three patients had clinically Significant atheromatous embolization. It is unclear what the long-term restenosis rate will be for renal artery stenting for ostial disease. However, some investigators believe the results will be improved by overexpanding the renal altery stent and using intraarterial ultrasound to ensure that the stent is properly deployed. It is important to allow the stent to extend into the aorta 1 or 2 mm in patients with ostial disease. Renal artery stenting is an excelJent procedure for patients with advanced atherosclerosis who are at high risk for surgical revascularization. Clearly, the technology for diagnosing ASO-RAD has advanced considerably. Surgical and endovascular methods for renal revascularization have been used with a high degree of technical success in some medical centers. Despite these observations, and the increasing enthusiasm for renal revascularization to avert or reverse renal insufficiency, the hypothesis that ASO-RAD progresses in most patients, despite adequate blood pressure control, with resulting loss of renal function, and that overall renal function can be preserved in the long term by successful renal revascularization remains unproved. A single-center prospective controlled clinical trial is in progress at the Cleveland Clinic, which eventually may determine whether ASO-RAD is a correctable cause of renal failure. Finally, several unresolved issues remain regarding the wide-spread application of interventional approaches to these patients: Can we be certain that
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ASO-RAD is, indeed, a progressive disorder? What is the optimal time to intervene to preserve renal function in patients with progressive azotemia? That is, is there a window of opportunity within which one should intervene, and at what point is it too early or too late to intervene? In patients with controlled blood pressure and mild degrees of renal insufficiency, is an aggressive approach to preserve renal function justified? Considering the risks involved with such patients, should our attention be directed to detecting and treating ASO-RAD with a view toward removing patients from dialysis Cend-stage renal disease) rather than to intervening under the assumption that nonoperated or nondilated ASO-RAD eventually will progress to renal insufficiency and end-stage renal disease' Finally, how many patients are actually receiving dialysis consequent to ASO-RAD? Although the information reviewed herein suggests a favorable influence of interventional therapy on the natural history of ASO-RAD, future studies in this area must include controlled clinical trials that compare patients with similar degrees of ASO-RAD managed concurrently with nonoperative therapy. Prospective evaluations of P1'RA and renal artery stents and surgical revascularization should be evaluated and compared rigorously.
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41. Clair DG, Belkin M, Whittemore AD, et al. Safety and efficacy of transaortic renal endalterectomy as an adjunct to aortic surgely. ] Vasc Surg 1995; 21:926-33 [with a discussion on p 934]. 42. Hansen KJ, et at. Surgical management of dialysisdependent ischemic nephropathy. J Vasc Surg 1995; 21:197-211. 43. Olin JW, et al. The utility of duplex scanning of the renal arteries for diagnosing significant renal artery stenosis. Ann Intern Med 1995; 122:833-838. 44. Topol EJ, Nissen SE. Our preoccupation with coronary luminology; the dissociation between clinical and angiographic findings in ischemic heart disease. Circulation 1995; 92:2333-2342. 45. Cambria RP, Brewster DC, L'ltalien GJ, et al. Renal artery reconstruction for the preservation of renal function. J Vasc Surg 1996; 24:37]-80 [with a discussion on pp 380-382]. 46. Erdoes LS, Berman SS, Hunter GC, MiJls JL. Comparative analysis of percutaneous transluminal angioplasty and operation for renal revascularization. Am J Kidney Dis 1996; 27:496-503. 47. Zierler RE, Bergelin RO, Davidson RC, et at. A prospective study of disease progression in patients with atherosclerotic renal artery stenosis. Am] Hypertens 1996; 9:1055-1061. 48. Blum U, Krumme B, Flugel P, et at. Treatment of ostial renal-artelY stenoses with vascular endoprostheses after unsuccessful baJloon angioplasty. N Engl J Med 1997; 336:459-465. 49. Harden PN, Macleod M], Rodger RSC, et al. Effect of renal-artery stenting on progression of renovascular renal failure. Lancet 1997; 349;1133-1136. 50. Pohl MA. Renal artery stenosis, renal vascular hypertension and ischemic nephropathy. In Schrier RW, Gottschalk CW, eds. Diseases of the Kidney, 6th ed. Boston: Little, Brown and Company, 1997, pp 13671425 51. Tullis MJ, Zierler RE, Glickerman DJ, et at. Results of percutaneous transluminal angioplasty for atherosclerotic renal artery stenosis: a follow-up study with duplex ultrasonography.] Vasc Surg 1997; 25:46-54. 52. Caps MT, Zierler RE, Polissar NL, et al. Risk of atrophy in kidneys with atherosclerotic renal artery stenosis. Kidney Int 1998; 53:735-742. 53. Fiala LA, Jackson MR, GiJlespie DL, et at. Primary stenting of atherosclerotic renal artery ostial stenosis. Ann Vasc Surg 1998; 12:128-133.
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54. Plouin PF, Chatellier G, Dame B, Raynaud A, for the Essai Multicentrique Medicaments vs. Angioplastie (EMMA) Study Group. Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a randomized trial. Hypertension 1998; 31:823-829. 55. Textor Sc. Revasularization in atherosclerotic renal artery disease. Kidney Int 1998: 53:799-811. 56. van de Yen P]G, Beutler ]], Katee R, et al. Angiotensin converting enzyme inhibitor-induced renal dysfunction in atherosclerotic renovascular disease. Kidney Int 1998; 53:986-993. 8:20 am Noninvasive Diagnosis of Renal Artery Stenosis: Which Test to Use When Berrzard F. King, Jr., MD Mayo Clinic Rochester, Minnesota
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Learning objectives: (1) List thefour noninvasive techniques being used for the evaluation of renovascular hypertension; (2) Give the strengths and weaknesses of captopril renography in the evaluation of renovascular hypertension; (3) Give the strengths and weaknesses of color Doppler sonography in the evaluation of renovascular hypertension; (4) Give the strengths and weaknesses of CT angiography in the evaluation of renovascular hypertension; (5) Give the strengths and weaknesses ofMR angiography in the evaluation of renovascular hypertension. More than 50 million people in the United States are hypertensive. Renovascular disease may account for up to 5% of these hypertensive patients. Because renovascular hypertension is potentially curable, much effort has been devoted to detecting and treating patients with renal artery stenosis. Conventional angiography traditionally has been used to diagnose renal artery stenosis; because of its invasiveness and cost, however, conventional angiography usually is not used as a screening test in all patients who may have renal artery stenoses. Several noninvasive studies have been advocated for screening patients who may have renovascular hypertension. The most commonly used noninvasive screening examination techniques include Doppler sonography, captopril renography, computed tomographic (CT) angiography, and magnetic resonance (MR) angiography. Because the accuracy of these noninvasive studies is widely variable, a proper understanding and appropriate use of these noninvasive studies is mandatory. Choosing the appropriate noninvasive screening imaging study for renovascular disease begins with proper clinical evaluation. No single clinical finding is capable of consistently identifying patients with renovascular hypertension; however, several risk factors can suggest the possibility of renovascular disease. These include onset of hypertension under the age of 30 or after the age of 50, abrupt onset at any time, hypertension refractory to medical therapy, grade 3 or 4 retinopathy, epigastric
bruit, deterioration of renal function after angiotensin converting enzyme (ACE) inhibitor therapy, and generalized arterial sclerotic disease with hypertension. Proper identification of these clinical findings can lead to more advantageous use of noninvasive screening examinations for renovascular hypertension. Duplex Doppler Sonography Duplex Doppler sonography is an attractive noninvasive screening test because it is relatively inexpensive, does not require intravascular contrast medium, and can be used in patients with any level of renal function. As with many of the noninvasive imaging examinations, there have been numerous reported parameters and abnormal criteria indicating possible renovascular disease. The most often quoted parameters are peak systolic velocities in the renal artery exceeding 100-200 crn/sec or a renal artery/aortic peak systolic velocity ratio exceeding 3.5. By using these parameters, early investigators have quoted sensitivities from 85% to 90%. Specificities were also quite high, in the range of 95%. However, many investigators have had trouble duplicating these results, and some have reported extremely poor sensitivity, as low as 0%. A major problem in many of these studies is that approximately 10% to 20% of patients undergoing duplex Doppler exams of the renal arteries have technically inadequate studies secondary to obesity or overlying bowel gas. These patients often are eliminated from statistical analysis in the aforementioned studies. In addition, examinations reported in various studies have varied in length, from 10 to 15 minutes up to 90 minutes. This variability in examination time, technical expertise, and super-selection of patients has contributed to the variability in sensitivity rates reported in the literature. Recent reports have advocated velocity waveform analysis of the segmental renal arteries in the kidneys. These smaller vessels are more consistently identified through a flank approach, allOWing for a consistent exam even in obese patients and in patients with anterior abdominal bowel gas. By using upper, middle, and lower pole segmental artery velocity waveform analysis in the kidneys, one can evaluate the waveform appearance and determine if there is a dampened peak systolic velocity (parva) or a delay in peak systolic velocity (tarda). If the parva and/or tarda waveform occurs in these segmental arteries, it indicates a more prOXimal artery stenosis. Early reports demonstrated a sensitivity of 85% to 90% in the detection of renal artery stenosis using these segmental artery waveform analyses. Subsequent studies, however, have not been able to duplicate such high sensitivities with this technique. It now appears evident that Doppler sonographic analysis of the renal arteries for the detection of renal artery stenosis should include velocity waveform analysis of both the main renal artery and the segmental renal arteries in both kidneys. Combining both the main renal artery and segmental altery waveform analysis will offer the highest sensitivity in .the detection of renal artery